Type-IA variations: questions and answers

  • Email
  • Help

Once a veterinary product has received approval from the Commission (the “Commission Decision”) all further procedures connected with the product will fall under “Post-Authorisation Procedures”.

This guidance provides an overview for a number of procedures that occur frequently and addresses a number of questions which Marketing Authorisation Holders (MAHs) may have.

More information on this post-authorisation procedural advice Q&A.

As of 1 January 2017 it is mandatory for applicants to use the eSubmission Gateway / Web Client for all veterinary procedural submissions to the Agency. For more information, including links to guidance on registration with the system, see:

Additional information

Back to top

1. When shall I submit my Type IA/IAIN variation(s)?

Commission Regulation (EC) No 1234/2008 (‘the Variations Regulation’) and the “Commission guideline on the details of the various categories of variations” (‘the Classification Guideline’) set out a list of changes to be considered as Type IA variations. Such minor variations have only a minimal impact, or no impact at all, on the quality, safety or efficacy of the medicinal product, and do not require prior approval before implementation (“Do and Tell” procedure). The Classification Guideline clarifies the conditions which must be met in order for a change to be considered a Type IA variation.

Such minor variations are classified in two subcategories, which impact on their submission:

  • Type IA variations  requiring immediate notification (‘IAIN’)

The Classification Guideline specifies which Type IA variations must be notified (submitted) immediately to the National Competent Authorities/European Medicines Agency (‘the Agency’) following implementation, in order to ensure the continuous supervision of the medicinal product.

  • Type IA variations  NOT requiring immediate notification (‘IA’)

Variations which do not require immediate notification may be submitted by the marketing authorisation holder (MAH) within 12 months after implementation, or may be submitted earlier should this facilitate dossier life-cycle maintenance or when necessary e.g. to ensure that the latest product information is reflected in Certificates of Medicinal Products.

The 12 month deadline to notify minor variations of Type IA allows for an ‘annual reporting’ for these variations, where a MAH submits several minor variations of Type IA which have been implemented during the previous twelve months.

Most of these Type IA variations do not impact on the product information. However, in case of an upcoming submission of a variation, extension or other regulatory procedure which will affect the product information, the MAH should also include any Type IA change(s) affecting the product information, in order to keep the product information up-to-date and to facilitate document management.

There are no recommended submission dates for Type IA. However, MAHs are encouraged to avoid submitting Type IA notifications shortly before or during the Agency holiday periods (e.g. end July and Christmas).

Meaning of “implementation” for Type IA variations

For quality changes, implementation is when the Company makes the change in its own Quality System.

This interpretation allows companies to manufacture conformance batches and generate any needed stability studies to support a Type IAIN variation before making an immediate notification1 because the change will not be made in their own Quality System until these data are available.

For changes to the pharmacovigilance system (DDPS), ‘implementation’ is when the Company makes the change in its DDPS (i.e. when it internally approves the DDPS incorporating the changes).

For product information, it is when the Company internally approves the revised product information. The revised product information will then be used in the next packaging run.

1. For example the type IAIN for addition, deletion or replacement of components in the flavouring or colouring system requires stability data on at least two pilot scale or industrial scale batches.

References

2. Can I group the submission of Type IA/IAIN variations? Can they be grouped with other types of variations?

Article 7(2)(a) of the Variations Regulation sets-out the possibility for a MAH to group several Type IA/ IAIN variations under a single application to the same relevant authority, or to group them with other types of variations.

Possible grouping of Type IA/IAIN changes only:

  • Several Type IA or IAIN affecting one medicinal product.
  • This means for instance that a Type IA variation, which is normally not subject to immediate notification, can be included in the submission of a Type IAIN variation.
  • One Type IA or IAIN affecting several medicinal products from the same MAH. 

       

  • Several Type IA and/or IAIN affecting several medicinal products from the same MAH provided that those variations are the same for all medicinal products and are submitted to the same relevant authority.

Possible grouping of Type IA/IAIN with other types of variations:

  • Type IA/IAIN can also be grouped with other variations (e.g. Type IB, Type II, Extension).
  • Such grouped submissions will follow the timetable and review procedure of the highest variation in the group. Please also refer to “What type of variations can be grouped?”.

It must be noted however, that when submitting Type IA/IAIN variations as part of a group, the legal deadlines for submission of each variation should be respected i.e. a Type IAIN should always be submitted immediately, whether or not it is grouped with other variations, and any Type IA variation should always be submitted within 12 months following its implementation.

3. Is the (Co-) Rapporteur involved in the review of Type IA/IAIN variations?

The Agency will review the notification within 30 days following receipt, without involvement of the Rapporteur or Co-Rapporteur.

However, a copy of the complete Type IA/IAIN notification must be submitted to the Rapporteur (See also “How shall I present and submit my Type IA/IAIN Variation”).

The same principle applies whether a single or a group of Type IA/IAIN variations is being submitted.

However, if the Type IA/IAIN Variations are grouped with other variations (IB, II, extension), the grouped submission will follow the review procedure and timelines of the highest variation in the group and the Rapporteur will provide an assessment report for the group. Although the Rapporteur is not expected to assess the Type IA/IAIN variations in the group the Rapporteur will confirm in the assessment report whether non-acceptance of (part of) the change(s) in the group leads to non-acceptance of the Type IA/ IAIN changes in the group.

4. How shall I present and submit my Type IA/IAIN variation(s)? Rev. January 2017

In order to help marketing-authorisation holders ensure that their Type IA/IAIN variation applications are complete and correct before submitting them to the Agency, it is strongly recommended to use the pre-notification checklist.

The Commission “Guideline on the operation of the procedures laid down in Chapters II, III and IV of Commission Regulation (EC) No 1234/2008” (‘the Procedural Guideline’) further specifies which elements should be included in a Type IA/IAIN variation notification:

Cover letter (for groupings, include a short overview of the nature of the changes). The Agency has published a formatted table template to be inserted in cover letters, found here.

  • The completed EU variation application form (as published on the Commission’s website in Volume 6C of the Notice to applicants), including the details of the marketing authorisation(s) concerned, as well as a description of all variations submitted together with their date of implementation. Where a variation leads to or is the consequence of other variations, a description of the relation between these variations should be provided in the appropriate section of the application form. MAHs are reminded that the variation application form should be signed by the official contact person. Should the official contact person not be available, an official letter of authorisation confirming the delegation of signature to a different person should be enclosed. For a grouping affecting several medicinal products, MAHs are reminded to confirm in the application form under “Declaration of the applicant” that the MAs concerned belong to the same MAH and that the main signatory confirms authorisation to sign on behalf of the designated contacts.
  • Reference to the part of the Classification guideline, indicating that all conditions and documentation requirements are met, or reference to the published Article 5 Recommendation, if applicable, used for the relevant application.
  • All documentation as specified in the Commission Classification Guideline.
  • If applicable, the revised summary of product characteristics, labelling and/or package leaflet as a full set of annexes. (See also 10. When do I have to submit revised product information? In all languages?)
  • The EMA has also published a pre-notification checklist to assist applicants with their submissions.


Grouped Type IA/IAIN variations

For grouped Type IA/IAIN variations concerning one marketing authorisation, all Type IA variations must be declared in the variation application form. The supportive documentation for all variations concerned should be submitted as one integrated package (i.e. there is no need to submit a separate documentation package for each variation). However, the present-proposed section of the application form should clearly identify the relevant dossier sections in support of each variation.

For a (group of) Type IA/IAIN variation(s) concerning several marketing authorisations, a common cover letter and common application form referring to all medicinal products and variations concerned. In addition, for each medicinal product the relevant supportive documentation and revised product information (if applicable) should be provided, in order to allow the Agency to update the dossier of each marketing authorisation with the relevant updated/new information. Cross-references to any documentation submitted for another medicinal product can therefore not be accepted. For further details, please refer to “How shall I present a grouped variations application?”.

It should be noted that the responsibility for the quality of the submitted documentation lies with the MAH and is crucial to the overall process. The MAH is responsible for ensuring that the Type IA variation complies fully with the conditions and documentation requirements as specified in the Classification guideline.

Type IA variations are intended to provide for a simple, rapid and efficient procedure for minor changes. The MAH should be aware that the submission of redundant information or a confusing dossier presentation will not facilitate rapid procedures. Similarly, deficient and missing documentation can lead to rejection of the variation. The MAH can be requested to provide missing documentation during the review of the application. Not providing the requested information immediately on request of the Agency can lead to rejection of the variation.

For more detailed queries on technical and procedural matters related to a Type IA/IAIN Variation for a specific product and in order to avoid rejection, please contact vet.applications@ema.europa.eu

Submission of Type IA/IAIN variation applications

Type IA/IAIN variation applications should be addressed to vet.applications@ema.europa.eu.

One electronic copy of the variation application presented in the correct format should be submitted to the Agency.

Where applicable, revised product information Annexes should be included in electronic (Word and PDF) format (see also “When do I have to submit revised product information? In all languages?”).

From 1 January 2017 it will be mandatory for applicants to use the eSubmission Gateway / Web Client for all veterinary procedural submissions to the Agency. For more information, including links to guidance on registration with the system, see the Veterinary eSubmission website.

One copy should also be sent to the Rapporteur at the time of submission (for information).

Any electronic submissions should be made in accordance with the guideline on e-submissions.

References

5. How shall my Type IA/IAIN variation be handled (timetable)?

The Agency will review the (grouped) Type IA/IAIN variation(s) within 30 calendar days following receipt. The Agency will check the correctness of the application form, the presence of the required documentation and compliance with the required conditions, in accordance with the Classification guideline.

  • Receipt of Type IA/IAIN variation application Day 0
  • Start of Agency check Day 1
  • Favourable/Unfavourable review outcome by Day 30

By day 30, the Agency will inform the MAH by fax or Eudralink.

Where one or several Type IA/IAIN variations are submitted as part of one notification, the Agency will clearly inform the MAH which variation(s) have been accepted or rejected following its review.

Type IA/IAIN changes can be implemented prior to submission of the application. However, in case of an unfavourable outcome, the Variations Regulation requires the MAH to immediately cease applying the rejected variation(s). Please refer to “What should I do in case of an unfavourable review outcome for my type IA/IAIN variation?” for further details.

It is still possible for MAHs to submit Type IA application prior to its implementation, particularly when the proposed changes are related to other notifications/variations requiring prior approval.

6. Can my Type IA/IAIN be part of worksharing?

In accordance with the provisions of Article 20 of the Variations Regulation, the worksharing procedure does not apply to Type IA/IAIN variations.

However, the submission of one or several Type IA/IAIN variations affecting more than one marketing authorisation of the same MAH, in one application to the same relevant authority (similar to worksharing) is possible under Article 7(2) of the Regulation – see also “Can I group the submission of Type IA/IAIN variations? Can they be grouped with other types of variations?”

In addition, it is also possible to group a Type IA/IAIN variation(s) with a Type IB or Type II variation, which is submitted for a worksharing procedure. In such case, the review of the Type IA/IAIN variation will be performed as part of the worksharing procedure.

7. What should I do in case of an unfavourable outcome for my type IA/IAIN variation(s)?

A Type IA/IAIN variation will be rejected when not all of the conditions for the Type IA/IAIN variation are met, or when the submitted documentation as required by the Classification Guideline is deficient. In such case, the MAH shall immediately cease to apply the rejected changes.

In the case of a negative outcome of a Type IA application because the conditions for Type IA variation(s) are not met and consequently a resubmission (as a Type IB, Type II variation or Extension) is needed or because documentation is deficient, it is the MAH’s responsibility to judge whether the rejected Type IA variation has an impact on the quality, safety or efficacy of the medicinal product. If this is the case, the MAH has to take appropriate action.

The Agency may ask the MAH to complete a suspected quality defect notification form and provide a Risk Assessment report on the impact of the product on the market via e-mail to qdefect@ema.europa.eu within 7 calendar days from the date of the rejection letter. Such requests are expected to be very exceptional. The MAH should follow the instructions under Product Defects.

8. What fee do I have to pay for a Type IA/IAIN variation?

For information on the fees applicable for type-IA and -IAIN variations, please refer to fees payable to the European Medicines Agency. Such fees cover all authorised strengths, pharmaceutical forms and presentations of a given medicinal product.

Grouped type-IA or -IAIN variations, whether consequential or not, will each attract a separate type-IA fee.

The fee will become due on the date of receipt of the type-IA or -IAIN-variation notification and fees will be payable within 45 calendar days of the date of the said notification. After approximately 15 days, an invoice will be sent to the applicants billing address held on the Agency’s file.

The invoice will contain details of the product and type of procedure involved, the fee amount, the customer purchase order number associated with the procedures invoiced and financial information.

The Agency does not accept standalone notifications of purchase order numbers that are not associated with a dossier. Applicants not requiring a purchase order number on the invoice should also clearly state this in the cover letter. Applicants are requested to provide this information in the formatted table template

The Agency will charge the fee for type-IA variations or grouped type-IA variations at the start of the procedure, irrespective of its outcome (positive, negative, or partial or full withdrawal).

Type-IA variations that are grouped with other type of variations or extensions or which are part of a worksharing procedure will continue to be charged on conclusion of the validation of the application.

Reference

9. Do I have to submit mock-ups?

Where the Type IA/IAIN variation affects the labelling and/or package leaflet, no mock-ups are required to be provided with the application.

Where the overall design and readability of the outer and immediate packaging and/or package leaflet is affected by the change then a mock-up should be submitted.

Reference

10. When do I have to submit revised product information? In all languages?

Where the Type IA/IAIN application affects SPC, labelling and/or package leaflet, the affected revised product information Annexes must be submitted as follows:

  • All EEA language versions: complete set of Annexes electronically only in Word format (highlighted) and in PDF (clean)
  • The ‘complete set of Annexes’ includes Annex A (if applicable), I, II, IIIA and IIIB i.e. all authorised presentations (if applicable), SPC, labelling and PL texts for all strengths and pharmaceutical forms of the product concerned, as well as Annex II. The complete set of Annexes must be presented sequentially (i.e. Annex I, II, IIIA, IIIB) as one document for each official EU language. Page numbering should start with "1" (bottom, centre) on the title page of Annex I. The ‘QRD Convention’ published on the Agency website should be followed. When submitting the full set of Annexes in PDF format, this should be accompanied by the completed formatting checklist which provides guidance on how to correctly prepare the PDF versions.
  • The electronic copy of all languages should be provided as part of the variation application on CD-ROM/DVD or via Eudralink. Highlighted changes should be indicated via ‘Tools – Track Changes’. Clean versions should have all changes ‘accepted’.
  • Icelandic and Norwegian language versions must always be included.
  • The Annexes provided should only reflect the changes introduced by the Variation(s) concerned. However, in exceptional cases where MAHs take the opportunity to introduce minor linguistic amendments in the texts this should be clearly mentioned in the cover letter and in the scope section of the application form.
    In addition, the section “present/proposed” in the application form should clearly list the minor linguistic amendments introduced for each language. Alternatively, such listing may be provided as a separate document attached to the application form. Any changes not listed, will not be considered as part of the variation application. In such cases, and in cases where any other ongoing procedure(s) may affect the product information Annexes, the MAH is advised to contact the Agency in advance of submission or finalisation of the procedure(s) concerned.
  • For Type IA/IAIN variations affecting Annex A (e.g. introduction of a new presentation), translations of the revised Annex A in all EU languages should be provided as separate documents in clean Word and PDF format, together with the variation application. Where the variation introduces a new EU sub-number, the new sub-number should be included in the Annex A and in the product information texts as part of the variation application (see also “How to obtain new EU sub-numbers for a Type IAIN variation concerning an additional presentation (e.g. new pack-size)”?). Similarly, in case of a deletion of a pharmaceutical form/strength/pack-size(s), the amended Annex A and product information Annexes should be provided as part of the Variation application.
11. How and when will the updated product information Annexes become part of the Marketing Authorisation?

For Type IA/IAIN variations affecting the product information Annexes to the Commission Decision, the Commission Decision will be updated within 12 months.

By the end of this period, the Agency will send the complete set of Annexes, based on the latest (previously) approved Annexes and reflecting the Type IA/IAIN change(s) agreed, together with a line-listing of those Type IA/IAIN application(s). The Commission will subsequently issue a Commission Decision on the Type IA/IAIN application(s) concerned.

However, where any Opinion affecting the Annexes is transmitted to the Commission within these 12 months, the changes of the Type IA/IAIN application(s) concerned will already be included in the Annexes to that Opinion and will consequently be reflected in the resulting Commission Decision.This Commission Decision will therefore replace the 12-monthly updating of the MA for the Type IA/IAIN application(s) concerned.

On the occasion of the next Type IA/IAIN variation affecting the Annexes, the procedure outlined above will be repeated based on the new ‘Reference point’ of the next Type IA/IAIN concerned (see also diagram below, which illustrates the 12-monthly updating process.

In addition, it is important that in case of an upcoming submission of a variation, extension or other regulatory procedure which will affect the product information, the MAH should also include any Type IA change(s) affecting the product information that have not been previously notified, in order to keep the product information up-to-date and to facilitate document management.

Where a Type IA/IAIN application concerns several marketing authorisations, the Commission will update the marketing authorisation with one Decision per marketing authorisation concerned.

12. How do I obtain new EU sub-numbers for a Type IAIN variation concerning an additional presentation (e.g. new pack-size)? June 2015

In the specific case of a Type IAIN variation for an additional presentation, the new EU marketing authorisation sub-number should be requested from the Agency before implementation.

The request should be sent together with a draft Annex A (in English only) to vet.applications@ema.europa.eu with a copy to the product shared mailbox and should be made at least 5 working days in advance of the intended submission of the variation. Once a number has been allocated, this number should subsequently be included in the Annex A and product information annexes submitted together with the Variation notification.

13. What should be the date of revision of the text for Type IA variations?

Type IA/IAIN variations do not require prior approval before implementation (“Do and Tell” procedure), i.e. they can be implemented and notified to the Agency either immediately for Type IA variations requiring immediate notification (‘IAIN’) or within 12 months for Type IA variations not requiring immediate notification (‘IA’).

For Type IA variations affecting the product information, the date of revision of the text to be included in section 10 of the summary of product characteristics and in the corresponding section of the package leaflet at the time of printing should be the date of implementation of the change by the Marketing Authorisation Holder.

The meaning of “implementation” is explained in question and answer: 1. When shall I submit my Type IA/IAIN variation(s)?

14. What can be considered an editorial change and how can it be submitted as part of a Type IA/IB/II variation? - New June 2016

General principles

The European Commission’s ‘Variations Guidelines’ 2013/C 223/01 specify that “If amendments to the dossier only concern editorial changes, such changes should generally not be submitted as a separate variation, but they can be included in a variation concerning that part of the dossier. In such cases the changes should be clearly identified in the application form as editorial changes and a declaration that the content of the concerned part of the dossier has not been changed by the editorial changes beyond the scope of the variation submitted should be provided”. Changes that can be classified as a variation according to the Variations Guidelines are not considered editorial changes and should be submitted under the appropriate variation category.

In practice “that part of the dossier” (referred to above) can be taken to mean concerning Parts 2, 3 or 4, as appropriate.

Editorial changes should generally not be submitted as a separate variation and therefore no reference to a variation category is required when they are encompassed within another variation procedure.

Within the section of the variation application form under the section on ‘Precise scope and background…’, the MAH should provide:

  • a brief description of the proposed editorial changes and a justification as to why they are considered ‘editorial’ (i.e. why they should not trigger a specific variation);
  • a declaration confirming that the changes proposed as editorial do not change the content of the concerned part(s) of the dossier beyond the scope of the variation within which the editorial changes are being submitted;
  • confirmation that all relevant parts of the dossier have been updated accordingly and are included within the variation package.

Additionally all the editorial changes should be listed in the present/proposed table (or provided as a separate annex that is cross-referred to from this table), identifying each related change in the dossier down the lowest section heading and page numbers where possible.

Any changes proposed by the applicants as editorial will be carefully considered by the Agency at time of submission and may be subject to further assessment at the same time as the variation. Proposed editorial changes that cannot be accepted as such will be rejected. In case of doubt, applicants can contact the Agency in advance of the planned submission using vet.applications@ema.europa.eu.

Editorial changes in Part 2 (quality)

The following may be considered as examples of editorial changes to Part 2: adding headers for ease of use, reordering of existing information without changing the meaning, alignment of information among/within the sections provided the correct reference that had been previously agreed can be demonstrated (e.g. alignment of information in flow charts to process description), punctuation changes and grammar/orthographic corrections that do not alter the meaning of the text.

Examples of changes that cannot be considered editorial: removal of specification parameters or manufacturing description, update of information to bring the dossier content in line with the current manufacturing process, etc.

Proposed changes that require confirmation by the rapporteur may only be accepted when submitted within the scope of an upcoming variation type IB or type II which impacts upon Part 2.

If editorial changes are required and there is no upcoming procedure, the MAH may consider submitting these changes as a separate, default Type IB variation (B.I.z or B.II.z, as appropriate).

Editorial changes in Parts 3 (safety & residues) and 4 (pre‑clinical & clinical)

Editorial changes in Parts 3 and 4 are not foreseen. Please contact vet.applicactions@ema.europa.eu in advance of an upcoming submission.

Editorial changes to the product information in Part 1.B (SPC, labelling and package leaflet)

Formatting changes, correction of typographical errors and/or mistakes to the English product information or other linguistic versions of the product information are considered editorial changes provided that the meaning of the text is not altered. These changes can be included within the scope of any upcoming procedure impacting on the product information.

Changes in the scientific content or meaning cannot be accepted as an editorial change. These changes should be classified under the scope of the relevant category as per the Variations Guidelines (e.g. Type II, C.I.4).

Proposed changes that may require confirmation by the Rapporteur or linguistic review will only be accepted when submitted within the scope of an upcoming variation type IB or type II which impacts upon the product information.

Should there be no upcoming regulatory procedure in which to include the editorial changes, these could also be submitted as a stand-alone, default Type IB variation e.g. under C.I.z if they affect the English product information. If other languages are affected and in case no procedure affecting the product information is upcoming, holders are advised to contact vet.applications@ema.europa.eu to discuss how to handle these necessary changes.

The MAH should liaise with the Agency without delay if the mistake concerns an incorrect or missing important information (e.g. contra-indication or adverse event) that could affect the safe and effective use of the medicinal product and/or lead to a potential medication errors (e.g. wrong strength, wrong posology, wrong route of administration).

References

15. What is considered to be a non-significant in-process control or specification parameter? - New February 2017

Variation scopes B.I.a.4.c, B.I.b.1.d, B.I.c.2.c, B.II.b.5.c, B.II.c.1.c, B.II.d.1.d, B.II.e.2.c and B.IV.2.f of the Variations guidelines 2013/C 223/01, deal with the deletion of a non-significant in-process control (IPC) test or specification parameter. Provided all relevant conditions and documentation requirements are met, all these variations fall under the Type IA category (do-and-tell).

For the categories listed above and other variations related to specifications of active ingredients, excipients, finished product, packaging material or measuring or administration device, the deletion of an obsolete parameter is given as an example. For finished products, this is further exemplified by mentioning of odour and taste. Although it is not possible to give similar examples for all of the categories mentioned above, these examples serve as an indication of the types of changes considered to fall under this variation category, regardless if this is related to in-process controls or specifications. This is therefore intended to be used for truly obsolete tests that are no longer part of normal specifications for newer products, but have remained for historical reasons in older products.

This variation category is not intended to include changes in relation to revisions of the control strategy with an intention to minimise redundant testing of parameters and attributes (critical or non-critical) that are tested at different stages during the production, or cases where process/ product characterisation performed after authorisation has shown that the attribute/ parameter is non-critical. Such changes require regulatory assessment and are to be handled as Type IB or II variations as appropriate.

16. When applying for a new pack size, what is considered within the range/outside the range (classification category B.II.e.5)? - New June 2017

The introduction of a new pack size (i.e. additional to currently approved pack sizes) should be submitted as a variation under subindent B.II.e.5.a) according to the variations classification guidelines.

Range is defined from the smallest to the biggest approved pack size (not from ‘0’) for the same pharmaceutical form and strength. The pack size equals to the number of units of the pharmaceutical form (e.g. tablets, sachets, ampoules, etc.) contained per outer packaging. Pack sizes not included within this range are considered to be outside of the range.

For the addition of a new pack size where the number of units of the pack is within the range of the currently approved pack sizes for the strength and pharmaceutical form, applicants should submit a variation B.II.e.5.a.1 (IAIN).

For the addition of a new pack size where the number of units of the pack is outside the range of the currently approved pack sizes for the strength and pharmaceutical form, applicants should submit a variation B.II.e.5.a.2 (IB).

In support of a timely introduction of new pack sizes to the market, the EMA accepts the following approach for the introduction of various pack sizes falling outside the range within a single grouped submission. The biggest or the smallest pack size per strength outside the range should be classified as B.II.e.5.a.2 (IB). This presentation defines the new limits of the range so that any intermediate pack size for the strength and pharmaceutical form can be classified as B.II.e.5.a.1 (IAIN).

Some examples are provided below to illustrate the principles explained above.

Example 1

The 20 mg strength of ‘Veterinary Medicinal Product A’ currently has two approved pack sizes of 30 and 60 tablets for the pharmaceutical form ‘film-coated tablets’ and the MAH intends to apply for a new pack size of 45 tablets. The introduction of a new pack size of 45 tablets for the 20 mg strength is considered within the range of approved packs (30-60 tablets) and should be classified as variation B.II.e.5.a.1 (IAIN).

Example 2

The 20 mg strength of ‘Veterinary Medicinal Product A’ currently has two approved pack sizes of 30 and 60 tablets for the pharmaceutical form ‘film-coated tablets’ and the MAH intends to apply for a new pack size of 90 tablets. The introduction of a new pack size of 90 tablets for the 20 mg strength is considered outside the range of approved packs (30-60 tablets)and should be classified as variation B.II.e.5.a.2 (IB).

Example 3

The 20 mg strength of ‘Veterinary Medicinal Product A’ currently has two approved pack sizes of 30 and 60 tablets for the pharmaceutical form ‘film-coated tablets’ and the MAH intends to apply for two new pack sizes of 90 and 120 tablets at the same time. The introduction of a new pack size of 120 tablets for the 20 mg strength is considered outsidethe range of packs and should be classified as variation B.II.e.5.a.2 (IB). This pack size defines a new limit for the range (30-120), so that the introduction of a pack size of 90 tablets can be classified as a variation B.II.e.5.a.1 (IAIN). The MAH should therefore apply for a grouped variationof 1 x type IB - B.II.e.5.a.2 and 1 x type IAIN - B.II.e.5.a.1.

Example 4

The 20 mg and 40 mg strengths of ‘Veterinary Medicinal Product B’ currently each have two approved pack sizes of 2 and 10 pre-filled syringes for the pharmaceutical form ‘solution for injection’. The MAH intends to apply for four new pack sizes:

  • 5 and 30 pre-filled syringes for the 20 mg strength;
  • 5 and 30 pre-filled syringes for the 40 mg strength

For the 20 mg strength, the introduction of a new pack size of 5 pre-filled syringes strength is considered within the range of approved packs (2-10)and should be classified as variation B.II.e.5.a.1 (IAIN) and the introduction of a new pack size of 30 pre-filled syringes is considered outsidethe range of approved packs (2-10) and should be classified as variation B.II.e.5.a.2 (IB).

For the 40 mg strength, the introduction of a new pack size of 5 pre-filled syringes strength is considered within the range of approved packs (2-10)and should be classified as variation B.II.e.5.a.1 (IAIN) and the introduction of a new pack size of 30 pre-filled syringes is considered outsidethe range of approved packs (2-10)and should be classified as variation B.II.e.5.a.2 (IB).

The MAH should therefore apply to the EMA for a grouped variation for the abovementioned scopes.

Example 5

The 50 mg strength of ‘Veterinary Medicinal Product C’ currently has two approved pack sizes of 10 and 30 tablets for the pharmaceutical form‘film coated tablets’ and the MAH intends to apply for a multipackof 30 (3x10) tablets. The introduction of a multipack 30 (3x10) tablets for the 50 mg strength is considered within the range of approved packs (10-30) and should be classified as variation B.II.e.5.a.1 (IAIN).

Important

  • For variations introducing additional presentations or pack sizes, each additional presentation or pack size attracts separate fees (x additional presentations = x separate fees). Each presentation and pack size should therefore be declared as a separate variation on the variation application form under the section ‘variations included in this application’.
  • Changes to strength, pharmaceutical form and route of administration are to be submitted as an extension of a marketing authorisation.
  • For additional guidance on changes to existing presentation that can trigger new EU number(s) please see Q10, Q11 and Q15 of the EMA’s regulatory guidance for human medicinal products on Type IA, Type IB and Type II variations, respectively.

How helpful is this page?

Average rating:

 Based on 20 ratings

Add your rating:

See all ratings
3 ratings
3 ratings
4 ratings
2 ratings
8 ratings
    

Tell us more